Changes in brain white matter integrity after systemic treatment for breast cancer: a prospective longitudinal study: a prospective longitudinal study

S. Menning, M.B. de Ruiter, D.J. Veltman, W. Boogerd, H.S.A. Oldenburg, L. Reneman, S.B. Schagen

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An increasing number of studies suggest chemotherapy for breast cancer may be neurotoxic. Cross-sectional MRI diffusion tensor imaging (DTI) studies suggest a vulnerability of brain white matter to various chemotherapeutic regimens. Up till now, this was confirmed in one prospective DTI study: Deprez et al. (2012) showed a widespread decline in fractional anisotropy (FA) of breast cancer patients after chemotherapy consisting of 5-fluorouracil (5-FU), epirubicin and cyclophosphamide (FEC) +/− taxanes +/− endocrine treatment. Our aim was to evaluate whether similar detrimental effects on white matter integrity would be observed with the currently widely prescribed anthracycline-based chemotherapy for breast cancer (predominantly doxorubicin and cyclophosphamide +/− taxanes +/− endocrine treatment (=BC + SYST; n = 26) compared to no systemic treatment (BC; n = 23) and no-cancer controls (NC; n = 30). Assessment took place before and six months after chemotherapy, and matched intervals for the unexposed groups. DTI data were analyzed using voxel-based tract-based spatial statistics and region of interest (ROI) analysis. Voxel-based analysis did not show an effect of chemotherapy +/− endocrine treatment on white matter integrity. ROI analysis however indicated subtle detrimental effects of chemotherapy +/− endocrine treatment by showing a larger decline in WM integrity in the superior longitudinal fasciculus and corticospinal tract in BC + SYST than BC. Indications for relatively mild neurotoxicity in our study might be explained by patient characteristics and specific aspects of data analysis. The omission of 5-FU in current treatment regimens or the administration of doxorubicin instead of epirubicin is also discussed as an explanation for the observed effects.
Original languageEnglish
Pages (from-to)324-334
Number of pages11
JournalBrain Imaging and Behavior
Issue number2
Early online date13 Mar 2017
Publication statusPublished - 1 Apr 2018


  • Breast cancer
  • CRCI
  • Cancer related cognitive impairment
  • Chemotherapy
  • Cognition
  • Diffusion tensor imaging (DTI)
  • Neurotoxicity
  • Side effects
  • White matter

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